Canonical BMP signaling in tubular cells mediates recovery after acute kidney injury

Vigolo, Emilia; Markó, Lajos; Hinze, Christian; Müller, Dominik N.; Schmidt‐Ullrich, Ruth; Schmidt‐Ott, Kai M.

doi:10.1016/j.kint.2018.08.028

Cited by 43 publications

(35 citation statements)

References 58 publications

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“…Earlier studies showed that the expression of Id2 protein is closely related to fibrosis in mouse proximal renal tubular cells. With the development of EMT, the expression of Id2 decreased significantly (Gervasi et al, 2012;Vigolo et al, 2019). Our results also found that compared with the wild-type mice, the expression of Id2 in renal tissue of db/db mice decreased significantly, and the level of Twist increased significantly.…”

Section: Discussionsupporting

confidence: 70%

Oxymatrine Inhibits Twist-Mediated Renal Tubulointerstitial Fibrosis by Upregulating Id2 Expression

et al. 2020

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The final pathway for the development of diabetic nephropathy (DN) into chronic renal failure in DN is glomerulosclerosis and tubulointerstitial fibrosis. Renal tubular lesions can occur in the early stage of DN renal injury. Cumulative evidence shows that oxymatrine (OMT) has a variety of biological and pharmacological properties. In recent years, more attention has been paid on the preventive and therapeutic influence of OMT on organ fibrosis. In this experiment, db/db mice were intraperitoneally injected with OMT 120 mg/kg for 8 weeks, and NRK-52E cultured with 30 mmol/L glucose and 0.1 mg/mL OMT for 48-hour. We investigated the relationship between Id2 and Twist in NRK-52E cells and the effect of OMT on the expression of E-cadherin, α-SMA, Fibronectin, and Collagen-IV by Western blot, Real-time PCR, Immunofluorescence, cell transfection, Co-Immunoprecipitation, and Luciferase assays. OMT increased the expression of Id2 but decreased that of Twist under high glucose condition in vitro and in vivo. The promoted recovery of Id2 facilitated its binding to Twist and affected E-cadherin activity inhibiting EMT and the excessive proliferation and abnormal deposition of ECM. In brief, OMT promotes Id2 to reverse EMT and exert anti-fibrotic effect in diabetic renal tubular epithelial cells by binding Id2 to Twist and affecting its transcriptional activation of downstream target genes. Or findings provide a new experimental basis for delaying the progress and for treatment of diabetic renal fibrosis.

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Section: Discussionsupporting

confidence: 70%

Oxymatrine Inhibits Twist-Mediated Renal Tubulointerstitial Fibrosis by Upregulating Id2 Expression

et al. 2020

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“…SMAD family member 2 (Smad2) and Smad3 play a critical role in TGFb1-mediated epithelial-mesenchymal transition (EMT). 29 Treatment with rhTM significantly suppressed the activation of Smad2 and Smad3 in TGFb1-TG mice compared with untreated TG mice ( Figure 8c) and in human podocytes cultured in the presence of TGFb1 (Supplementary Figure S20C). 29 Figure S21A and B).…”

Section: Gpr15 Mediationmentioning

confidence: 90%

Thrombomodulin ameliorates transforming growth factor-β1–mediated chronic kidney disease via the G-protein coupled receptor 15/Akt signal pathway

Takeshita

Yasuma

Nishihama

et al. 2020

Kidney International

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Kidney fibrosis is the common consequence of chronic kidney diseases that inexorably progresses to end-stage kidney disease with organ failure treatable only with replacement therapy. Since transforming growth factor-b1 is the main player in the pathogenesis of kidney fibrosis, we posed the hypothesis that recombinant thrombomodulin can ameliorate transforming growth factor-b1-mediated progressive kidney fibrosis and failure. To interrogate our hypothesis, we generated a novel glomerulus-specific human transforming growth factor-b1 transgenic mouse to evaluate the therapeutic effect of recombinant thrombomodulin. This transgenic mouse developed progressive glomerular sclerosis and tubulointerstitial fibrosis with kidney failure. Therapy with recombinant thrombomodulin for four weeks significantly inhibited kidney fibrosis and improved organ function compared to untreated transgenic mice. Treatment with recombinant thrombomodulin significantly inhibited apoptosis and mesenchymal differentiation of podocytes by interacting with the G-protein coupled receptor 15 to activate the Akt signaling pathway and to upregulate the expression of anti-apoptotic proteins including survivin. Thus, our study strongly suggests the potential therapeutic efficacy of recombinant thrombomodulin for the treatment of chronic kidney disease and subsequent organ failure.

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“…The action of bone morphogenetic protein (BMP), which also belongs to the TGF protein family, in the kidney is not completely understood. In healthy renal tubules, BMP is constitutively active and its reactivation, after an injury that suppressed BMP expression, correlates with functional recovery [47].…”

Section: Molecular Mechanisms In Hypertensive Kidney Injurymentioning

confidence: 99%

Molecular Mechanisms of Kidney Injury and Repair in Arterial Hypertension

Sievers

Eckardt

2019

IJMS

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The global burden of chronic kidney disease is rising. The etiologies, heterogeneous, and arterial hypertension, are key factors contributing to the development and progression of chronic kidney disease. Arterial hypertension is induced and maintained by a complex network of systemic signaling pathways, such as the hormonal axis of the renin-angiotensin-aldosterone system, hemodynamic alterations affecting blood flow, oxygen supply, and the immune system. This review summarizes the clinical and histopathological features of hypertensive kidney injury and focusses on the interplay of distinct systemic signaling pathways, which drive hypertensive kidney injury in distinct cell types of the kidney. There are several parallels between hypertension-induced molecular signaling cascades in the renal epithelial, endothelial, interstitial, and immune cells. Angiotensin II signaling via the AT1R, hypoxia induced HIFα activation and mechanotransduction are closely interacting and further triggering the adaptions of metabolism, cytoskeletal rearrangement, and profibrotic TGF signaling. The interplay of these, and other cellular pathways, is crucial to balancing the injury and repair of the kidneys and determines the progression of hypertensive kidney disease.

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Canonical BMP signaling in tubular cells mediates recovery after acute kidney injury

Cited by 43 publications

References 58 publications

Oxymatrine Inhibits Twist-Mediated Renal Tubulointerstitial Fibrosis by Upregulating Id2 Expression

Oxymatrine Inhibits Twist-Mediated Renal Tubulointerstitial Fibrosis by Upregulating Id2 Expression

Thrombomodulin ameliorates transforming growth factor-β1–mediated chronic kidney disease via the G-protein coupled receptor 15/Akt signal pathway

Molecular Mechanisms of Kidney Injury and Repair in Arterial Hypertension

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